IUPAC Name
2-Methoxy-N-(1-phenethylpiperidin-4-yl)-N-phenylacetamide
Current Scheduling Status
Schedule I of the 1961 Convention on Narcotic Drugs
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Ortho-fluorofentanyl (N-(2-fluorophenyl)-N-[1-(2-phenylethyl)piperidin-4-yl] propanamide) is a synthetic analogue of the opioid analgesic fentanyl. It has two positional isomers (para-fluorofentanyl and meta-fluorofentanyl).
WHO review history
Ortho-fluorofentanyl has not been previously pre-reviewed or critically reviewed by the WHO ECDD. A direct critical review was proposed based on information brought to WHO’s attention that ortho-fluorofentanyl poses a serious risk to public health and has no recognized therapeutic use.
Similarity to known substances and effects on the central nervous system
Receptor binding data show that ortho-fluorofentanyl has a higher affinity to μ-opioid receptors than to κ- and δ-opioid receptors. No animal or human studies have been published in the scientific literature. However, the clinical features present in non-fatal cases of intoxication include characteristic opioid effects such as loss of consciousness, pupil constriction and respiratory depression. The effects of ortho-fluorofentanyl can be reversed by the administration of the opioid antagonist naloxone, further confirming its opioid agonist mechanism of action.
Dependence potential
No studies of the dependence potential of ortho-fluorofentanyl in humans or laboratory animals have been reported. However, based on its mechanism of action, it would be expected to produce dependence similar to other opioid drugs.
Actual abuse and/or evidence of likelihood of abuse
No animal or human studies are available to assess the abuse liability of ortho- fluorofentanyl. There is evidence of its use from several countries, including seizures in Europe and the United States. A number of confirmed fatalities have been reported associated with this substance (one in Europe and 16 in the United States since 2016). As a consequence of ortho-fluorofentanyl cross- reacting with standard fentanyl immunoassays, it is possible that deaths due to ortho-fluorofentanyl have been attributed to fentanyl and hence the number of recorded deaths due to ortho-fluorofentanyl may be an underestimate. Several countries in different parts of the world have placed ortho-fluorofentanyl under national control.
Therapeutic usefulness
Ortho-fluorofentanyl is not known to have any therapeutic use.
Recommendation
Ortho-fluorofentanyl is an opioid receptor agonist that has the potential for dependence and is subject to abuse. The limited evidence available indicates that it produces typical opioid adverse effects that include the potential to cause death due to respiratory depression. Ortho-fluorofentanyl has caused substantial harm and has no therapeutic use. It is liable to similar abuse and produces similar ill- effects to those of many other opioids placed in Schedule I of the 1961 Single Convention on Narcotic Drugs:
■■ Recommendation: The Committee recommended that ortho- fluorofentanyl (N-(2-fluorophenyl)-N-[1-(2-phenylethyl)piperidin- 4-yl]propanamide) be added to Schedule I of the 1961 Single Convention on Narcotic Drugs.
Ortho-fluorofentanyl (N-(2-fluorophenyl)-N-[1-(2-phenylethyl)piperidin-4-yl] propanamide) is a synthetic analogue of the opioid analgesic fentanyl. It has two positional isomers (para-fluorofentanyl and meta-fluorofentanyl).
WHO review history
Ortho-fluorofentanyl has not been previously pre-reviewed or critically reviewed by the WHO ECDD. A direct critical review was proposed based on information brought to WHO’s attention that ortho-fluorofentanyl poses a serious risk to public health and has no recognized therapeutic use.
Similarity to known substances and effects on the central nervous system
Receptor binding data show that ortho-fluorofentanyl has a higher affinity to μ-opioid receptors than to κ- and δ-opioid receptors. No animal or human studies have been published in the scientific literature. However, the clinical features present in non-fatal cases of intoxication include characteristic opioid effects such as loss of consciousness, pupil constriction and respiratory depression. The effects of ortho-fluorofentanyl can be reversed by the administration of the opioid antagonist naloxone, further confirming its opioid agonist mechanism of action.
Dependence potential
No studies of the dependence potential of ortho-fluorofentanyl in humans or laboratory animals have been reported. However, based on its mechanism of action, it would be expected to produce dependence similar to other opioid drugs.
Actual abuse and/or evidence of likelihood of abuse
No animal or human studies are available to assess the abuse liability of ortho- fluorofentanyl. There is evidence of its use from several countries, including seizures in Europe and the United States. A number of confirmed fatalities have been reported associated with this substance (one in Europe and 16 in the United States since 2016). As a consequence of ortho-fluorofentanyl cross- reacting with standard fentanyl immunoassays, it is possible that deaths due to ortho-fluorofentanyl have been attributed to fentanyl and hence the number of recorded deaths due to ortho-fluorofentanyl may be an underestimate. Several countries in different parts of the world have placed ortho-fluorofentanyl under national control.
Therapeutic usefulness
Ortho-fluorofentanyl is not known to have any therapeutic use.
Recommendation
Ortho-fluorofentanyl is an opioid receptor agonist that has the potential for dependence and is subject to abuse. The limited evidence available indicates that it produces typical opioid adverse effects that include the potential to cause death due to respiratory depression. Ortho-fluorofentanyl has caused substantial harm and has no therapeutic use. It is liable to similar abuse and produces similar ill- effects to those of many other opioids placed in Schedule I of the 1961 Single Convention on Narcotic Drugs:
■■ Recommendation: The Committee recommended that ortho- fluorofentanyl (N-(2-fluorophenyl)-N-[1-(2-phenylethyl)piperidin- 4-yl]propanamide) be added to Schedule I of the 1961 Single Convention on Narcotic Drugs.
ECDD Recommendation
Inclusion in Schedule I of the 1961 Convention on Narcotic Drugs
Link to full TRS
9789241210270-eng.pdf453.93 KB
MS Questionnaire Report